Abstract
Purpose: CD8 cytotoxic T cells (CTLs) play a critical role in the clearance of virally infected cells. SARS-CoV-2-specific CD8 T cells and functional CTLs in natural infections and following COVID-19 vaccine in primary antibody deficiency (PAD) have not been reported. In this study, we evaluated T cell response following COVID-19 or COVID-19 mRNA vaccination in patients with PADs by assessing SARS-CoV-2 tetramer-positive CD8 T cells and functional CTLs.
Methods: SARS-CoV-2-specific CD8 and functional CTLs were examined in a patient with X-linked agammaglobulinemia (XLA) and a patient with common variable immunodeficiency (CVID) following COVID-19 infection, and in 5 patients with CVID and 5 healthy controls 1 month following 2nd dose of COVID-19 mRNA vaccine (Pfizer-BioNTech). Cells were stained with SARS-CoV-2 spike protein-specific tetramers, and for functional CTLs (CD8 + CD107a + granzyme B + perforin + ), with monoclonal antibodies and isotype controls and analyzed by flow cytometry.
Results: SARS-CoV-2-specific tetramer + CD8 T cells and functional CTLs in the patient with XLA following COVID-19 infection were higher, as compared to healthy control subject following COVID-19 infection. On the other hand, SARS-CoV2-tetramer + CD8 T cells and functional CTLs were lower in CVID patient following COVID19 infection as compared to healthy control following COVID-19 infection. SARS-CoV2-tetramer + CD8 T cells and functional CTLs were significantly lower in SARS-CoV2-naive CVID patients (n = 10) following vaccination when compared to SARS-CoV-2-naive healthy vaccinated controls (n = 10).
Conclusions: CVID is associated with reduced SARS-CoV-2-specific CD8 T cells and functional CTLs in both natural SARS-CoV-2 infection and in response to SARS-CoV-2 mRNA vaccine, whereas natural infection in XLA is associated with a robust SARS-CoV-2-specific CD8 and functional CTL responses.
Keywords: CTLs; CVID; Pfizer/BNT vaccine; SARS-CoV-2-specific CD8 T cells; XLA.
【저자키워드】 CVID, XLA., CTLs, Pfizer/BNT vaccine, SARS-CoV-2-specific CD8 T cells, 【초록키워드】 COVID-19, SARS-CoV-2, COVID19, COVID-19 vaccine, vaccination, mRNA vaccine, SARS-COV-2 infection, monoclonal antibody, Infection, immunodeficiency, CD8, flow cytometry, COVID-19 infection, Patient, Control, natural infection, Critical, Pfizer-BioNTech, T cell response, CTL, SARS-CoV-2 spike, granzyme B, dose, X-linked agammaglobulinemia, CD8 T cell, Cytotoxic T cell, XLA, COVID-19 mRNA Vaccination, deficiency, subject, healthy control, infected cells, CD107a, clearance, significantly lower, responses, primary antibody, robust, analyzed, examined, healthy, reported, the patient, evaluated, reduced, functional, isotype control, patients with CVID, were stained, 【제목키워드】 CD8, response, natural, cytotoxic,